Changes in P2Y6 receptor‐mediated vasoreactivity following focal and global ischemia
Abstract Ischemia, both in the form of focal thromboembolic stroke and following subarachnoid hemorrhage (SAH), causes upregulation of vasoconstrictive receptor systems within the cerebral vasculature. Descriptions regarding changes in purinergic signaling following ischemia are lacking, especially...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-04-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.15283 |
| _version_ | 1817991651557113856 |
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| author | André Erdling Sara Ellinor Johansson Aneta Radziwon‐Balicka Saema Ansar Lars Edvinsson |
| author_facet | André Erdling Sara Ellinor Johansson Aneta Radziwon‐Balicka Saema Ansar Lars Edvinsson |
| author_sort | André Erdling |
| collection | DOAJ |
| description | Abstract Ischemia, both in the form of focal thromboembolic stroke and following subarachnoid hemorrhage (SAH), causes upregulation of vasoconstrictive receptor systems within the cerebral vasculature. Descriptions regarding changes in purinergic signaling following ischemia are lacking, especially when the importance of purinergic signaling in regulating vascular tone is taken into consideration. This prompted us to evaluate changes in P2Y6‐mediated vasomotor reactivity in two different stroke models in rat. We used wire myography to measure changes in cerebral vasoreactivity to the P2Y6 agonist UDP‐β‐S following either experimental SAH or transient middle cerebral artery occlusion. Changes in receptor localization or receptor expression were evaluated using immunohistochemistry and quantitative flow cytometry. Transient middle cerebral artery occlusion caused an increase in Emax when compared to sham (233.6 [206.1–258.5]% vs. 161.1 [147.1–242.6]%, p = 0.0365). No such change was seen following SAH. Both stroke models were associated with increased levels of P2Y6 receptor expression in the vascular smooth muscle cells (90.94 [86.99–99.15]% and 93.79 [89.96–96.39]% vs. 80.31 [70.80–80.86]%, p = 0.021) and p = 0.039 respectively. There was no change in receptor localization in either of the stroke models. Based on these findings, we conclude that focal ischemic stroke increases vascular sensitivity to UDP‐β‐S by upregulating P2Y6 receptors on vascular smooth muscle cells while experimental SAH did not induce changes in vasoreactivity in spite of increased P2Y6 receptor expression. |
| first_indexed | 2024-04-14T01:16:01Z |
| format | Article |
| id | doaj.art-99961fd0157d43be9c10dd9f5a45b722 |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-04-14T01:16:01Z |
| publishDate | 2022-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-99961fd0157d43be9c10dd9f5a45b7222022-12-22T02:20:52ZengWileyPhysiological Reports2051-817X2022-04-01108n/an/a10.14814/phy2.15283Changes in P2Y6 receptor‐mediated vasoreactivity following focal and global ischemiaAndré Erdling0Sara Ellinor Johansson1Aneta Radziwon‐Balicka2Saema Ansar3Lars Edvinsson4Department of Clinical Sciences Division of Experimental Vascular Research Lund University Lund SwedenDepartment of Clinical Experimental Research Glostrup Research Institute Rigshospitalet‐Glostrup Glostrup DenmarkDepartment of Clinical Experimental Research Glostrup Research Institute Rigshospitalet‐Glostrup Glostrup DenmarkApplied Neurovascular Research Department of Clinical Sciences Lund University Lund SwedenDepartment of Clinical Sciences Division of Experimental Vascular Research Lund University Lund SwedenAbstract Ischemia, both in the form of focal thromboembolic stroke and following subarachnoid hemorrhage (SAH), causes upregulation of vasoconstrictive receptor systems within the cerebral vasculature. Descriptions regarding changes in purinergic signaling following ischemia are lacking, especially when the importance of purinergic signaling in regulating vascular tone is taken into consideration. This prompted us to evaluate changes in P2Y6‐mediated vasomotor reactivity in two different stroke models in rat. We used wire myography to measure changes in cerebral vasoreactivity to the P2Y6 agonist UDP‐β‐S following either experimental SAH or transient middle cerebral artery occlusion. Changes in receptor localization or receptor expression were evaluated using immunohistochemistry and quantitative flow cytometry. Transient middle cerebral artery occlusion caused an increase in Emax when compared to sham (233.6 [206.1–258.5]% vs. 161.1 [147.1–242.6]%, p = 0.0365). No such change was seen following SAH. Both stroke models were associated with increased levels of P2Y6 receptor expression in the vascular smooth muscle cells (90.94 [86.99–99.15]% and 93.79 [89.96–96.39]% vs. 80.31 [70.80–80.86]%, p = 0.021) and p = 0.039 respectively. There was no change in receptor localization in either of the stroke models. Based on these findings, we conclude that focal ischemic stroke increases vascular sensitivity to UDP‐β‐S by upregulating P2Y6 receptors on vascular smooth muscle cells while experimental SAH did not induce changes in vasoreactivity in spite of increased P2Y6 receptor expression.https://doi.org/10.14814/phy2.15283MCAOP2Y6purinergicratSAHstroke |
| spellingShingle | André Erdling Sara Ellinor Johansson Aneta Radziwon‐Balicka Saema Ansar Lars Edvinsson Changes in P2Y6 receptor‐mediated vasoreactivity following focal and global ischemia Physiological Reports MCAO P2Y6 purinergic rat SAH stroke |
| title | Changes in P2Y6 receptor‐mediated vasoreactivity following focal and global ischemia |
| title_full | Changes in P2Y6 receptor‐mediated vasoreactivity following focal and global ischemia |
| title_fullStr | Changes in P2Y6 receptor‐mediated vasoreactivity following focal and global ischemia |
| title_full_unstemmed | Changes in P2Y6 receptor‐mediated vasoreactivity following focal and global ischemia |
| title_short | Changes in P2Y6 receptor‐mediated vasoreactivity following focal and global ischemia |
| title_sort | changes in p2y6 receptor mediated vasoreactivity following focal and global ischemia |
| topic | MCAO P2Y6 purinergic rat SAH stroke |
| url | https://doi.org/10.14814/phy2.15283 |
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